1.Research progress on hepatic macrophages and liver fibrosis
Haiyan JIANG ; Fangfang ZHONG ; Junping ZHANG
Journal of Pharmaceutical Practice and Service 2024;42(4):135-140
Liver fibrosis is a repair response to chronic liver injury caused by various etiologies. Its continuous progression can develop into liver cirrhosis or even hepatocellular carcinoma, eventually leading to liver failure. Currently, there is no effective treatment for liver fibrosis. Hepatic macrophages play a key role in intrahepatic inflammatory response, progression and resolution of fibrosis, and have emerged as an important therapeutic target for anti-hepatic fibrosis. The function of hepatic macrophages in the process of liver fibrosis was mainly reviewed and the mode of action of hepatic macrophages from various aspects was discussed to provide ideas for the treatment of liver fibrosis.
2.Upregulation of α1-acidglycoprotein to ameliorate hepatocyte lipid accumulation by Astragaloside derivative HHQ16
Xiang LI ; Xianmin DAI ; Xia LIU ; Yang SUN
Journal of Pharmaceutical Practice and Service 2024;42(4):141-146
Objective To investigate the effect and mechanism of HHQ 16, a derivative of astragaloside Ⅳ, on hepatocyte lipid accumulation. Methods Free fatty acids were used to stimulate lipid hepatocyte accumulation. Triglyceride and Oil Red O staining were detected to reflect hepatocyte lipid accumulation. The expression of α1-acidglycoprotein (ORM) and its regulators were detected by real-time quantitative PCR and immunoblotting. The expression of ORM1 was interfered with siRNA to determine whether it mediated the action of HHQ16.The expression of ORM1 was interfered by siRNA to determine whether it mediated the action of HHQ16. Results HHQ16 significantly ameliorated FFA-induced hepatocyte lipid deposition. HHQ16 elevated ORM expression, and the protective effect of HHQ16 on hepatocyte lipid accumulation was reversed by ORM interference. Conclusion HHQ16 could ameliorate hepatocyte lipid accumulation by elevating ORM.
3.Genotoxicity evaluation of HMS-01
Yi CHEN ; Qingyan SUN ; Xiang LI ; Yang SUN ; Xia LIU
Journal of Pharmaceutical Practice and Service 2024;42(4):147-150
Objective To provide a toxicological basis for HMS-01 in future clinical trials, through genotoxicity testing of safety evaluation. Methods The genotoxicity of HMS-01 was evaluated by Bacterial Reverse Mutation Assay (Ames test) with Salmonella typhimurium. Results HMS-01 was non-mutagenic against Salmonella typhimurium at six doses of 20.6, 61.7, 185.2, 555.6, 1666.7, and 5000 μg/dish with (or without) a metabolic activation system. Conclusion HMS-01 was not found to be mutagenic in the dose range of this experiment.
4.Study on antifungal effect of demethylzelamaldehyde in vitro
Lei HAN ; Hua ZHONG ; Xinrong WANG ; Yan WANG
Journal of Pharmaceutical Practice and Service 2024;42(4):151-156
Objective To study the antifungal effect of demethylzelamaldehyde in vitro. Methods The minimum inhibitory concentrations (MIC) of demethylzeylasteral and fluconazole against 23 fungal strains were determined by micro liquid dilution method. The synergistic index (FICI) of the two drugs was determined using a checkerboard micro liquid dilution method. The synergistic effect of the combination of the two drugs was visually verified by paper diffusion experiments. Finally, the cytotoxicity of demethylzelamaldehyde was determined by CCK-8 method. Results Demethylzelamaldehyde showed a broad spectrum of antifungal activity when used alone, with MICs ranging from 4 g/L to 32 g/L. When combined with fluconazole, the effective concentration of fluconazole could be reduced from over 64 g/L to 0.25 g/L, with FICI values ranging from 0.129 to 0.254, indicating the synergistic effect of the two drugs. The CCK-8 results showed that demethylzeylasteral exhibited cytotoxicity only at concentrations four times higher than the MIC value. Conclusion Demethylzelamaldehyde exhibited good antifungal effect and synergistic effect with fluconazole, and its toxicity was low.
5.Potential mechanism of Babao Dan in the treatment of hepatocellular carcinoma based on network pharmacology
Xinyu ZHU ; Haoran BAI ; Naping ZHAO ; Dachuan QI ; Lixin WEI ; Li ZHANG
Journal of Pharmaceutical Practice and Service 2024;42(4):157-164
Objective To explore the potential mechanism of Babao Dan on primary liver cancer based on network pharmacology. Methods First, the diethylnitrosamine-induced hepatocellular carcinoma rat(HCC)model was used to observe the effects of Babao Dan. Then, the effective components in Babao Dan were detected by UPLC-MS, and the potential target sites of these effective components were predicted in the Swiss Target Prediction databases, etc. The corresponding target sites for HCC were screened using GeneCards, OMIM and Therapeutic Target Database, and the common target sites between Babao Dan and HCC were obtained after getting the intersection. The protein-protein interaction network was drawn by Cytoscape software and the STRING database, and the key molecules regulating HCC by Babao Dan were screened out. The effective target sites were subjected to GO analysis in the DAVID database and enrichment analysis in the Pathway’s KEGG. Finally, the clinical relevance of key molecules to liver cancer patients was verified by the TCGA database. Results Babao Dan could slow down the tumor development. 851 chemical components were detected in BaBao Dan by UPLC-MS , 9 major active components and 285 target sites were identified. 637 hepatocellular carcinoma-related targets were screened out, and 16 targets of Babao Dan regulating HCC were identified. GO enrichment analysis showed 802 biological processes, 11 cell compositions, and 43 molecular functions, while KEGG pathway enrichment analysis identified a total of 90 pathways. Correlation analysis of TCGA identified three key molecules associated with the survival of liver cancer patients. Conclusion In the primary rat liver cancer model, Babao Dan was found to significantly prolong the survival of cancer-induced rats and reduce tumor burden. The initial prediction of the mechanism by which Babao Dan regulating liver cancer was made through UPLC-MS analysis and network pharmacology methods, indicating that Babao Dan has the characteristics of multi-component, multi-pathway, and multi-target regulation of primary liver cancer, which could provide a reference for further relevant experimental research.
6.The increasement of blood METRNL protein by insulin sensitizer rosiglitazone
Fei XU ; Jin CHEN ; Zhiyong LI
Journal of Pharmaceutical Practice and Service 2024;42(4):165-168
Objective To investigate the effect of insulin sensitizer rosiglitazone on blood METRNL levels. Methods After fed with high fat diet (HFD) for 3 months, obese mice were treated with rosiglitazone for 1 month. Glucose tolerance was tested with glucose tolerance test (GTT), and METRNL levels in blood were measured by ELISA. Real time fluorescence quantitative PCR was used to detect the expression of METRNL in various tissues such as muscle, liver, white fat, brown fat, brain, spleen and kidney, as well as the expression of mitochondrial proteins in brown adipose tissue. Results Glucose tolerance of animals fed a high-fat diet was improved in rosiglitazone group, and blood METRNL levels were also increased significantly in this group. Rosiglitazone treatment increased the expression of METRNL in brown fat and kidney tissue. There was no effect on METRNL expression in muscle, liver, white fat, brain and spleen. Rosiglitazone increased the expression of mitochondrial-associated proteins in brown adipose tissue. Conclusion The insulin sensitizer rosiglitazone might increase the serum METRNL level by increasing the METRNL expression in brown fat and kidney tissue, suggesting that METRNL may be involved in the therapeutic effect of rosiglitazone on diabetes.
7.Analysis of tissue distribution of metabolites in Crocus sativus L. corms based on DESI mass spectrometry imaging technique
Xi CHEN ; Xingguang XIE ; Kunmiao FENG ; Yingjie LU ; Ting HAN
Journal of Pharmaceutical Practice and Service 2024;42(4):169-172
Objective To explore the distribution characteristics of endogenous metabolites in Crocus sativus L. corms from different origins. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. sativus corms. Results In situ characterization of metabolites such as flavonoids, organic acids, amino acids, carotenoids, and cyclic enol ether terpene glycosides was achieved. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Apigenin 7-(6''-O-acetyl)-glucoside, isorhamnetin-3-O-β-D-Glucoside, dhurrin 6'-glucoside, and Apigenin 7-O-diglucuronide were mainly distributed in the terminal bud. For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. Conclusion The distribution of metabolites in different parts of C. sativus corms from different origins and the same origin varies significantly. Flavonoids and flavonoid derivatives such as isorhamnetin-3-O-β-D-Glucoside and apigenin derivatives are mainly distributed in the terminal buds, in addition, the natural plant protection agent dhurrin 6'-glucoside is also mainly distributed in the terminal corms, whereas amino acids, which are used as energy and material supplies, are mainly accumulated in the corms.
8.Mechanisms of Shexiang Baoxin Pill in homo-therapy for heteropathy in type 2 diabetes mellitus and coronary heart disease based on network pharmacology
Zifan ZHU ; Zhicong WANG ; Bin XIE ; Runhui LIU
Journal of Pharmaceutical Practice and Service 2024;42(4):173-180
Objective To probe into the mechanism of Shexiang Baoxin Pill in homo-therapy for heteropathy for type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) based on network pharmacology. Methods All chemical components and action targets of these seven traditional Chinese medical in Shexiang Baoxin Pill were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM platform, and the DisGeNET and GeneCards databases were used to obtain CHD and T2DM-related Disease targets. The “drug-component-target” network map was constructed by Cytoscape 3.8.2 software, the protein-protein interaction (PPI) network map was constructed by STRING database, and the GO biological process analysis and KEGG pathway enrichment analysis were performed on the common targets of Shexiang Baoxin Pill for T2DM and CHD using DAVID online database. Results A total of 101 potential active ingredients for the treatment of T2DM and CHD in Shexiang Baoxin Pill were screened out, corresponding to 229 targets. Network analysis results showed that the common main active ingredients in Shexiang Baoxin Pill for treating T2DM and CHD might be chenodeoxycholic acid, ursodeoxycholic acid, cinnamic aldehyde, bile acids, cinnamic acid, and ginsenosides. The results of pathway enrichment analysis showed that the mechanism of action of Shexiang Baoxin Pill in the treatment of type 2 diabetes and coronary heart disease in treating T2DM and CHD might be related to the inhibition of inflammatory response and oxidative stress. Conclusion Shexiang Baoxin Pill could play a role in treating CHD and T2DM through multiple components, multiple targets and multiple pathways, which provided a certain theoretical basis for the clinical application and further research of Shexiang Baoxin Pill.
9.The latest research progress of α7 nicotinic acetylcholine receptor in cholinergic anti-inflammatory pathway
Huimin ZHANG ; Kefa XIANG ; Xiaofei SHI ; Zhen QIN ; Xia LIU
Journal of Pharmaceutical Practice and Service 2022;40(6):485-493
α7 nicotinic acetylcholine receptor (α7nAChR) belongs to nicotinic acetylcholine receptors (nAChRs), which is the key receptor in cholinergic anti-inflammatory pathway and plays an important role in the neural regulation of immune system. Recent studies have found that α7nAChR is also involved in the regulation of various physiological and pathological processes other than immunity, such as non-alcoholic fatty liver, angiogenesis, heart protection, etc. In addition, α7nAChR is closely related to energy metabolism in neurodegenerative diseases. This article reviews the role of α7nAChR in treating inflammation and improving energy metabolism, and the new direction of α7nAChR involved in therapy.
10.Study on polymorphism of peritoneal microbial community after laparoscopic exploration in New Zealand rabbits based on 16S rDNA sequencing
Pingping ZHANG ; Wenbin WU ; Qi CAO ; Zhuo QU ; Pei WANG
Journal of Pharmaceutical Practice and Service 2022;40(6):494-498
Objective To explore the polymorphism of microbial community after laparoscopic abdominal exploration by using bacterial 16s ribosomal DNA (16S rDNA) sequencing technology. Methods New Zealand rabbits were divided into model group and control group. The rabbits in the model group were operated by portable laparoscopy, and the rabbits in the control group were not treated. One week later, the peritoneal effusions of the model group and the control group were taken for 16S rDNA sequencing to analyze the microbial community polymorphism. To explore the changes of microbial community in peritoneal effusion in the model group compared with the control group. Results After 16S rDNA sequencing, bioinformatics was used to determine the microbial communities. Inter group difference analysis showed a good similarity of microbial communities between the two groups. OTU taxonomic analysis and species composition analysis (Rank-Abundance curve and Venn diagram) found that the microbial community level of the model group was significantly higher than that of the control group. Alpha diversity analysis (Sobs, Ace, Shannon, Simpson) showed that the richness and diversity of microbial community in the model group were higher than those in the control group. Microbial composition analysis showed that the number of miscellaneous bacteria in the model group increased by about 30% compared with the control group. The species differences between the two groups were tested for significance. It was found that Pasteurellales, Neisseria and Tsukamurella increased significantly. Conclusion The diversity of microbial communities in peritoneal effusion increases after laparoscopic abdominal exploration in New Zealand rabbits, and the most significant increases are Pasteurella, Neisseria and Tsukamura.